DOPA AND HUNTINGTON'S DISEASE

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genic properties of Y-linked antigens increased by syner-gistic action with other weak histocompatibility antigens ofsimilar strength as has been shown in rodents 8,9; or hasthis immunogenetic relationship between mother and hermale fetus resulted in a placenta that is more predisposedto cellular exchange ? Recent observations in rats and micethat spermatozoa in small numbers introduced into theuterine lumen are potent immunogens as far as histo-

compatibility antigens are concerned hint at an alternativepossibility.1OThere have been many attempts to explain the observed

variation in the response of Rh-negative persons exposedto Rh antigens. It has been suggested that non-reactivityto Rh antigens might arise from the gestation of a Rh-negative female child in a Rh-positive mother, affordingthe fetus an opportunity to become tolerant of the antigensconcerned.l1 Thus a Rh-negative female child gestated ina Rh-positive mother should have an impaired capacityto form anti-D antibodies when in adult life she bears herfirst Rh-positive fetus, in comparison with a Rh-negativefemale gestated by a Rh-negative mother. However, thisingenious hypothesis has not been supported by factualevidence. In accord with clinical experience and evidencefor acquisition of the capacity to react against some anti-gens long before birth,12 it is just as likely that in-uterosensitisation of the Rh-negative fetus might result from thisexposure.

Since it has been claimed that 5°.-0 of Rh-negative infantsare indeed sensitised by their Rh-positive mothers," furtherresearch regarding the nature of factors leading to iso-immunisation during a first pregnancy is needed to deter-mine whether Rh-negative female infants born of Rh-

positive mothers should routinely be given prophylacticanti-D immune globulin.We wish to thank Jo Scott and Nancy Saunderson for their

help and Dr R. E. Billingham for his suggestions. This workwas supported in part by U.S.P.H.S. grant Al-10678 and theUniversity of Texas Southwestern Medical School RegentsAppropriation for Organized Research A/C 210005.

Departments of Cell Biology andObstetrics and Gynecology,

University of Texas SouthwesternMedical School,

Dallas, Texas 75235, U.S.A.JAMES R. SCOTTALAN E. BEER.

DOPA AND HUNTINGTON’S DISEASE

SIR,-Dr Baskin and Dr Rosenberg (March 17, p. 582)are to be congratulated on their stimulating venture intoscientific speculation. Their attempt to elucidate themolecular pathogenesis of Huntington’s chorea is praise-worthy in that it does focus upon the basic defect of thechoreic-the premature death of some of his caudateneurons. However, I feel that the devotion that they showto dopa (or dopamine, &c.) in ascribing to it so complex arole in this illness is scarcely justified.The basis of their case is that choreics, and perhaps

" pre-choreics ", have exaggerated symptoms when fedwith dopa. Certainly they appear to have such a response,but surely this is the result of increasing the neurotrans-mitter-like function of dopamine by raising its concentra-tion in the soup bathing the residual caudate neurons

8. Billingham, R. E., Silvers, W. K. The Immunobiology of Trans-plantation; p. 43. Englewood Cliffs, 1971.

9. Hildeman, W. H., Morgan, M., Frautnik, L. Transplant. Proc.1970, 2, 24.

10. Beer, A. E., Billingham, R. E. Advanc. Immun. 1971, 14, 1.11. Owen, R. D., Wood, H. R., Foord, A. G., Sturgeon, P., Baldwin,

L. G. Proc. natn. Acad. Sci. 1954, 40, 420.12. Silverstein, A. M., Parshall, C. J., Prendergast, R. A. in Ontogeny

of Immunity (edited by R. T. Smith, R. A. Good, and P. A.Miescher); p. 143. Gainesville, 1967.

13. Hindemann, P. Lancet, Jan. 6, 1973, p. 46.

rather than its effectiveness as an inhibitor of proteinsynthesis-and how long must protein synthesis beinhibited before the cell fails to work properly ? It appearsto take about 35 years to kill off a cell but only a few hoursat the least, days at the most, to make it sufficiently punchdrunk to be unable to function properly. It may be that

dopa/dopamine has long-term deleterious effects on the

disappearing caudate neuron, but it is scarcely justifiableto seek to substantiate this hypothesis on the basis ofobserved short-term effects.The invalidity of this premise, however, should not

detract from their valuable suggestion that examination ofenzyme activity of post-mortem material might helpelucidate a biochemical basis for cell death, but ratherincrease the range of aminoacid incorporations to bestudied. I hope that they will be able to perform theappropriate experiments to refute or confirm that defectiveprotein synthesis is the cause of loss of caudate neuronsand welcome the implication of their hypothesis that thesymptoms of the disease arise from cell loss rather thancell malfunction.

Department of Public Health andSocial Medicine,

University of Aberdeen,Aberdeen AB9 2ZD. G. A. VENTERS.

HUNTINGTON’S CHOREA AND LITHIUMTHERAPY

SiR,—Dalen reported 1 the successful treatment withlithium of patients with Huntington’s chorea (H.c.) andtardive dyskinesia. I have given lithium carbonate to fourpatients with H.c. and have performed cerebrospinal-fluid(C.s.F.) studies on three of them. Two patients improveddramatically, one clearly improved, and in the fourth

patient improvement was doubtful.Four patients with H.c., three women aged 47 (case 1), 45

(case 2), and 32 (case 3), and a man aged 42 (case 4) were studied.

C.S.F. LEVELS OF 5-H.I.A.A. AND H.V.A. BEFORE AND AFTER LITHIUMTREATMENT

The youngest had had symptoms for 2-3 years and was admittedto the psychiatric clinic for the drug trial, while the other threehad been from 5 to 10 years in a mental hospital. The threeoldest patients had mild dementia and striking hyperkinesia.They were all on neuroleptics. The youngest woman had onlyslight involuntary movements and a certain lack of judgmentindicating a personality change. She was not taking any drugs.Before lithium was given, objective recordings were made by an’ Animex’ activity measurer and a " brachio-kinesio-meter ".c.s.F. samples were taken under standardised conditions and5-hydroxyindoleacetic acid (5-H.I.A.A.) and homovanillic acid(H.v.A.) were analysed 11uorometrically.3.4 The dose of lithiumcarbonate was adjusted to keep the serum level between 0’5 and1-5 meq. per litre. C.S.F. samples and objective recordings weremade about 3 weeks after lithium treatment was started. Unfor-tunately some of the H.v.A. values were missed.The improvement became noticeable 7-10 days after lithium

treatment was started, and after about 3 weeks the improvementin the objective recordings was about 50% for cases 1 and 2,

1. Dalén, P. Lancet, Jan. 13, 1973, p. 107.2. Gottfries, C.-G., Gottfries, I., Olsson, E. Br.J. Psychiat. 1966, 112,

1269.3. Andén, N. E., Roos, B. E., Werdenius, B. Life Sci. 1963, 7, 448.4. Aschcroft, G. W., Sharman, D. F. Nature, 1960, 186, 1050.